The Peruvian bark was used for the treatment of intermittent fevers or ague and there was increased demand for powdered bark. In 1633, a study showed that not only was the remedy effective, but also there appeared to be no harmful properties. During the 17th century the Peruvian bark was used in almost every country in Europe; however, in one country, where the ague was a national calamity, it was shunned. The active component of the cinchona bark was unknown until isolated by Pierre Pelletier and Joseph Caventou in 1820. They began working on Peruvian bark in 1818. Instead of using gray bark, they worked with the yellow bark. The alcoholic extract did not produce a precipitate when diluted with water, and when alkali was added, it produced a pale yellow gummy substance that could be dissolved in ether, water, or alcohol; they named the bitter- tasting material quinine after the Indian word quina-quina. The cinchona alkaloids include cinchonine and cinchonidine, quinine and quinidine, and dihydroquinidine and dihydroquinine. Before the isolation of quinine itself, cinchona bark was administered according to the prescription of Talbor, i.e., in wine to disguise the bitter taste. The earliest record of lemonade containing quinine was in 1843 in New Orleans; Schweppes started volume manufacture of Indian tonic water in India in the 1870s and bitter lemon in 1957. For 350 years, quinine was the only effective drug against malaria, although it was not without side effects.